Neurofeedback Training for Relieving Auditory Hallucinations: How Should Neurofeedback Be Applied to AVHs? 4 Hypotheses

Simon McCarthy-Jones

Initial neurofeedback studies for SZ:AVH+ should target neural areas that have been reliably found to be associated with AVHs and which have been previously demonstrated to be amenable to neurofeedback. As the STG is the area most reliably associated with AVHs, and (healthy) individuals are able to use neurofeedback to regulate STG activity,^[30] this is the most promising target. Although the STG is activated during AVHs, it appears to be deactivated immediately preceding them. This raises the question as to whether learned upregulation or downregulation of the STG may be beneficial. It appears plausible that both may be. While during AVHs, the application of strategies to downregulate the activity of the STG may be beneficial, during the seconds immediately preceding AVHs, the application of strategies to upregulate the activity of the STG may be fruitful. The latter suggestion draws on a neurofeedback study^[31] which found that strategies to control cortical slow potentials leant by epileptic patients during EEG neurofeedback could be used by such patients when they felt a fit coming on in the real world, to prevent it. Although it may be queried how SZ:AVH+ could know when pre-AVH–related neural activity was occurring, many patients report sensing their AVHs coming on, or knowing triggers for their experiences (eg,^[32]). Another reason to suggest STG-upregulation before AVH-onset may be beneficial comes from studies showing less AVHs occurring in periods when SZ:AVH+ are humming,^[33] a task which has been shown to activate the STG (and IFG).^[34] Indeed, in addition to the STG, the IFG was also noted above as being reliably associated with AVHs (also being deactivated immediately before them but activated during them) and has been shown to be amenable to intentional modulation through neurofeedback.^[10] This leads to hypothesis 1:

Neurofeedback training will enable patients to learn to individually both upregulate and downregulate activity in their STG or IFG. Through the transfer effect, patients will then be able to apply the cognitive strategies that they have learnt to alter STG or IFG activation, during real-life occurrences of AVHs. Upregulating the STG or IFG when voices are experienced as about to begin should prevent their onset, and downregulating the STG or IFG when AVHs are already occurring, should reduce their severity.

A further hypothesis may be developed from TMS studies. Ros and colleagues5 found neurofeedback effect sizes comparable to excitability increases found using repetitive magnetic stimulation, suggesting that "whether endogenous or exogenous techniques are used, they appear to appeal to a common neural substrate"^(p777). Neurofeedback may hence be an alternative way of achieving TMS, but "from the inside." Indeed, neurofeedback could potentially be more effective than TMS. Whereas patients cannot practically have multiple TMS sessions each day, they could employ strategies learned from neurofeedback throughout their day. Furthermore, given TMS's artificial method of externally altering neural activity, internally induced changes created using strategies learned from neurofeedback may be able to utilize more natural methods, which the brain may be more receptive to. Hypothesis 2 is thus:

Neurofeedback training will enable patients with schizophrenia with AVHs to learn to modulate activity over their temporo-parietal junction (TPJ). Employing the strategies that they learn to be effective for modulating TPJ activity, will result in a reduction of the severity of their AVHs.

Could neurofeedback also be used to therapeutically address the neural connectivity issues reliably associated with AVHs? Although one study^[17] has found that neurofeedback training to increase insula activation in patients with schizophrenia led to connections between the insula cortex, amygdala and medial prefrontal cortex increasing, and new connections appearing between areas including the insula and anterior cingulate cortex (ACC), at present it has not been established whether neurofeedback can specifically increase connectivity in the arcuate fasciculus. A speculative hypothesis 3 is hence:

Carefully engineered neurofeedback can be used to repair connectivity abnormalities in patients with AVHs, across a range of neural circuits, reducing the severity of such patients' AVHs.

Finally, and also speculatively, it may be hypothesized that neurofeedback's demonstrated ability to cause affective/cognitive changes may be used to "repair" malfunctioning affective/cognitive mechanisms linked to AVHs. For example, given that impairments to both context memory, ie, the binding of events into memory, and the control of retrieval from memory are thought to play a causal role in the etiology of AVHs,^[35] it is possible that using neurofeedback to remedy this may help AVHs. As increasing power and synchrony in the gamma band through neurofeedback has been found to be associated with improved feature binding and control of memory retrieval,^[7,36] hypothesis 4 is:

EEG neurofeedback training aiming to increase power and synchrony in the gamma band will reduce the severity of AVHs

While the above hypotheses offer a promising research direction, there are some pertinent concerns. First, it is unclear how robust the transfer effect is, both in healthy individuals and in patients with schizophrenia.^[17] In one study, only half of ADHD patients who successfully undertook neurofeedback training could later achieve this in the scanner without any direct feedback.^[37] One way to mitigate this may be to screen SZ:AVH+, selecting only those who can perform a simple EEG neurofeedback task (such as modulating alpha frequency amplitudes) to go on to full neurofeedback training. Second, given the interindividual differences in neural activity associated with AVHs,^[38] as well as the potential for subtypes of AVHs to be associated with different neural signatures,^[39] optimal results may only be achieved by fMRI-guided neurofeedback (paralleling fMRI-guided TMS). Pilot work may wish to begin with relatively cheap, simple, and comfortable EEG neurofeedback and then build to individually designed fMRI-guided neurofeedback if such initial attempts prove unsuccessful. Alternatively, near-infrared spectroscopy neurofeedback may be a simpler method to begin piloting studies. Third, as most SZ:AVH+ spontaneously attempt to develop coping strategies for AVHs^[40] with only limited effectiveness, it may be asked why techniques learned from neurofeedback should be any more effective. Here, a neurofeedback study of chronic pain patients is informative.^[41] This study's chronic pain patients had attempted to find their own ways to cope with their pain but had not managed to do so. However, learning to directly control ACC activity using neurofeedback was effective in reducing their pain. Neurofeedback may therefore succeed where previous self-learned strategies have failed. A final caution is that if patients' AVHs have their roots in earlier traumatic events, there may be ethical implications for treating these in a solely neurological manner, without psychological (or even sociological) interventions.^[1]

If neurofeedback were to be effective for AVHs, a number of benefits would materialize. First, it would be preferable to TMS, which can be an unpleasant experience for some participants due to inadvertent motor activations. Second, following the rationale of cognitive behavioral therapy (CBT), it would allow patients to have a technique that they can take away and use themselves, which may be potentially empowering. Indeed, whereas TMS is a passive treatment which does not allow patients to experience the feeling that they themselves have overcome their AVHs, neurofeedback is an active process which, if effective, would allow patients to gain control over their AVH by their own efforts. Third, some patients report wanting to eliminate negative abusive AVHs yet to retain their friendly benevolent AVHs.^[42] Neurofeedback would allow patients to apply their eliminative strategies only during the occurrence of their negative voices and hence to retain their valued AVHs.